Oral testosterone tridecanoate therapy

ABSTRACT

The present disclosure provides methods and compositions for testosterone replacement therapy. The methods and compositions employ a fixed dose dosing regimen that does not require titration or dose adjustments and that can provide a therapeutically effective amount of a testosterone ester while avoiding unacceptably high testosterone levels.

PRIORITY DATA

This application is a continuation of U.S. application Ser. No.15/828,320, filed Nov. 30, 2017, which claims the benefit of U.S.Provisional Application Ser. No. 62/428,167, filed on Nov. 30, 2016, andU.S. Provisional Application Ser. No. 62/428,317, filed on Nov. 30,2016, each of which is incorporated herein by reference.

BACKGROUND

Most testosterone based pharmaceutical products on the market employdose titration schemes to ensure that patients are safely (e.g.,avoiding unacceptably high testosterone levels) and efficaciouslytreated (e.g., achieving typical eugonadal testosterone levels inhypogonadal patients). Dose titrations are typically required becausedifferent patients can absorb and metabolize testosterone based productsin substantially different manners. A dose of a testosterone product forone patient that provides safe and efficacious testosterone levels maynot provide safe and efficacious levels for another patient.

SUMMARY OF INVENTION

Disclosed herein is an oral testosterone therapy (“TT”) dosing regimen.In a specific aspect, the TT involves oral administration of a fixeddaily dose of a testosterone ester. For example, where the testosteroneester is testosterone tridecanoate (T13), a fixed dose within the rangeof 750-1150 mg per day (e.g., 840-1100 mg per day) of oral T13 isunexpectedly and particularly efficacious and safe for testosteronereplacement therapy (these doses can be provided once-a-day ortwice-a-day as a divided dose). Thus, in another example where thetestosterone ester is T13, the fixed daily dose can be provided as375-575 mg of oral T13 twice per day for a total daily dose of 750-1150mg T13. Surprisingly, these fixed dose regimens require no dosetitration to provide safe and efficacious serum testosterone levels to asubstantial proportion of subjects (e.g., those needing testosteronereplacement therapy). Thus, in some aspects, the fixed dose is providedas an oral pharmaceutical composition comprising a testosterone ester(e.g., testosterone tridecanoate) and a pharmaceutically acceptablecarrier, for once daily, or twice daily, etc. administration, with ameal or food, to a subject (e.g., a male having a condition associatedwith a deficiency or absence of endogenous testosterone).

In some embodiments, specific measures can be used to determine whetheror not the therapy should continue or be discontinued. For example,biomarkers such as consistency of unacceptable testosterone (T) levelsfrom a safety or efficacy standpoint, whether hematocrit levels riseabove a threshold value, whether Prostate Specific Antigen (“PSA”)levels rise above a threshold value, or any other appropriate measure ormarker can be used to determine whether the therapy should bediscontinued.

DETAILED DESCRIPTION OF INVENTION

Although the following detailed description contains many specifics forthe purpose of illustration, a person of ordinary skill in the art willappreciate that many variations and alterations to the following detailscan be made and are considered to be included herein. Accordingly, thefollowing embodiments are set forth without any loss of generality to,and without imposing limitations upon, any claims set forth. It is alsoto be understood that the terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to belimiting. Unless defined otherwise, all technical and scientific termsused herein have the same meaning as commonly understood by one ofordinary skill in the art to which this disclosure belongs.

As used in this specification and the appended claims, the singularforms “a,” “an,” and “the” include plural referents unless the contextclearly dictates otherwise. Thus, for example, reference to “polymer”can include a plurality of such polymers.

As used herein, “AUC” refers to the area under the serumconcentration-time curve

As used herein, “AUCt” refers to the area under the serumconcentration-time curve from time zero to time of last measurableconcentration.

As used herein, “C_(avg)” refers to average serum concentration over 24hours.

As used herein, “C_(max)” refers to maximum observed serum concentrationper dose over dosing interval.

As used herein, “T_(max)” refers to the time to maximum observed serumconcentration.

As used herein, “TT” refers to testosterone therapy. In a specificdefinition, TT means any condition wherein serum testosterone is belowthe normal eugonadal range, such as 300 ng/dL when measured on twoseparate occasions in the morning. In another definition, the TTdescribed herein can be used to treat patients that are eugonadal (orhypogonadal) for a condition other than specifically having testosteronelevels lower than 300 ng/dL. In another specific definition, TT refersto testosterone replacement therapy e.g., to treat a conditionassociated with a deficiency or absence of endogenous testosterone.

As used herein, “T equivalent dose” from a T13 dose is a testosteroneequivalent dose that can be released from the bioreversible T13 ester.For example, 168 mg of T13 is equivalent to 100 mg of T.

As used herein, “Eugonadal range” is the typical range of serumtestosterone found in patients not needing TT, normal eugonadal range,is defined as the range with an average testosterone lower limit of ˜300ng/dL and average testosterone upper limit of ˜1000 ng/dL. It isunderstood that this normal range could vary depending on thetestosterone assay utilized and variability among labs due to specificassay used by individual lab and patient demographics. Therefore, thelower limit of normal eugonadal range could also be 250 ng/dL.Similarly, the upper limit of normal eugonadal range could be 1040 or1100, or 1500 ng/dL.

As used herein, “dosing regimen” or administration regimen” can be usedinterchangeably and refer to specific dosing and administration of a T13containing product. In a specific embodiment, the dosing regimentypically entails daily dose, number of pills per dose, number of dosesper day, and whether or not to take with food or fasting. The dosingregimen can also provide relevant instructions regarding the above, forhealthcare providers and patients, in some embodiments. Some products(but not the product described herein) involve dose titration or a doseadjustment scheme, in patients needing adjustment, based on a patient'sresponse to the product assessed via measured T measured T levels postdosing at steady state. A practical dosing regimen is the one that iseasy to comprehend for implementation. The dosing regimen of thisinvention is a single fixed dose dosing regimen for TT that does notneed dose titration.

As used herein, “Fixed dose” refers to the same (e.g. unchanging) dailydose of testosterone tridecanoate being used for each patient throughouta therapy regimen with no dose changes. “Single,” “singular” or“unitary” fixed dose means that only one fixed daily dose (e.g., asdescribed herein elsewhere like one of 1000 mg T13 per day) oftestosterone tridecanoate is prescribed to a patient. No titrationneeded (or without titration) means for a given patient, the daily T13dose is not adjusted throughout the TT.

As used herein, “Discontinuation of TT” means the dosing regimen for thepatient is unsuitable for TT and should be temporarily stopped untilrelevant markers (e.g., biomarkers, T levels, or any other suitablemarker) improve or alternatively, it may be deemed that it ispermanently unsuitable for TT in the patient. As used herein,“Consistently” refers to at least two or more times or occurrences asmeasured on two separate occasions with a least a gap of 24 hourspreferably in the morning.

In this application, “comprises,” “comprising,” “containing” and“having” and the like can have the meaning ascribed to them in U.S.Patent law and can mean “includes,” “including,” and the like, and aregenerally interpreted to be open ended terms. The terms “consisting of”or “consists of” are closed terms, and include only the components,structures, steps, or the like specifically listed in conjunction withsuch terms, as well as that which is in accordance with U.S. Patent law.“Consisting essentially of” or “consists essentially of” have themeaning generally ascribed to them by U.S. Patent law. In particular,such terms are generally closed terms, with the exception of allowinginclusion of additional items, materials, components, steps, orelements, that do not materially affect the basic and novelcharacteristics or function of the item(s) used in connection therewith.For example, trace elements present in a composition, but not affectingthe compositions nature or characteristics would be permissible ifpresent under the “consisting essentially of” language, even though notexpressly recited in a list of items following such terminology. Whenusing an open-ended term, like “comprising” or “including,” in thiswritten description it is understood that direct support should beafforded also to “consisting essentially of” language as well as“consisting of” language as if stated explicitly and vice versa.

The terms “first,” “second,” “third,” “fourth,” and the like in thedescription and in the claims, if any, are used for distinguishingbetween similar elements and not necessarily for describing a particularsequential or chronological order. It is to be understood that any termsso used are interchangeable under appropriate circumstances such thatthe embodiments described herein are, for example, capable of operationin sequences other than those illustrated or otherwise described herein.Similarly, if a method is described herein as comprising a series ofsteps, the order of such steps as presented herein is not necessarilythe only order in which such steps may be performed, and certain of thestated steps may possibly be omitted and/or certain other steps notdescribed herein may possibly be added to the method.

As used herein, “subject” or “patient” are used interchangeably andrefer to a mammal that may benefit from the administration of acomposition described herein. In one aspect, the mammal may be a human.

As used herein, the terms “formulation” and “composition” are usedinterchangeably and refer to a mixture of two or more compounds,elements, or molecules. In some aspects, the terms “formulation” and“composition” may be used to refer to a mixture of one or more activeagents with a carrier or other excipients. Compositions can take nearlyany physical state, including solid and/or liquid (i.e. solution).Furthermore, the term “dosage form” can include one or moreformulation(s) or composition(s) provided in a form suitable foradministration to a subject.

As used herein, “effective amount” refers to an amount of an ingredientwhich, when included in a composition, is sufficient to achieve anintended compositional or physiological effect. Thus, a “therapeuticallyeffective amount” refers to a substantially non-toxic, but sufficientamount of an active agent, to achieve therapeutic results in treating orpreventing a condition for which the active agent is known to beeffective. It is understood that various biological factors may affectthe ability of a substance to perform its intended task. Therefore, an“effective amount” or a “therapeutically effective amount” may bedependent in some instances on such biological factors. Additionally, insome cases an “effective amount” or a “therapeutically effective amount”may not be achieved in a single dose. Rather, in some examples, an“effective amount” or a “therapeutically effective amount” can beachieved after administering a plurality of doses over a period of time,such as in a pre-designated dosing regimen. Further, while theachievement of therapeutic effects may be measured by a physician orother qualified medical person using evaluations known in the art, it isrecognized that individual variation and response to treatments may makethe achievement of therapeutic effects a subjective decision. Thedetermination of an effective amount is well within the ordinary skillin the art of pharmaceutical and nutritional sciences as well asmedicine.

As used herein, the term “substantially” refers to the complete ornearly complete extent or degree of an action, characteristic, property,state, structure, item, or result. For example, an object that is“substantially” enclosed would mean that the object is either completelyenclosed or nearly completely enclosed. The exact allowable degree ofdeviation from absolute completeness may in some cases depend on thespecific context. However, generally speaking, the nearness ofcompletion will be so as to have the same overall result as if absoluteand total completion were obtained. The use of “substantially” isequally applicable when used in a negative connotation to refer to thecomplete or near complete lack of an action, characteristic, property,state, structure, item, or result. For example, a composition that is“substantially free of” particles would either completely lackparticles, or so nearly completely lack particles that the effect wouldbe the same as if it completely lacked particles. In other words, acomposition that is “substantially free of” an ingredient or element maystill actually contain such item as long as there is no measurableeffect thereof.

As used herein, the term “about” is used to provide flexibility to anumerical range endpoint by providing that a given value may be “alittle above” or “a little below” the endpoint. Unless otherwise stated,use of the term “about” in accordance with a specific number ornumerical range should also be understood to provide support for suchnumerical terms or range without the term “about”. For example, for thesake of convenience and brevity, a numerical range of “about 50 mg toabout 80 mg” should also be understood to provide support for the rangeof “50 mg to 80 mg.” Furthermore, it is to be understood that in thiswritten description support for actual numerical values is provided evenwhen the term “about” is used therewith. For example, the recitation of“about” 30 should be construed as not only providing support for valuesa little above and a little below 30, but also for the actual numericalvalue of 30 as well.

As used herein, a plurality of items, structural elements, compositionalelements, and/or materials may be presented in a common list forconvenience. However, these lists should be construed as though eachmember of the list is individually identified as a separate and uniquemember. Thus, no individual member of such list should be construed as ade facto equivalent of any other member of the same list solely based ontheir presentation in a common group without indications to thecontrary.

Concentrations, amounts, and other numerical data may be expressed orpresented herein in a range format. It is to be understood that such arange format is used merely for convenience and brevity and thus shouldbe interpreted flexibly to include not only the numerical valuesexplicitly recited as the limits of the range, but also to include allthe individual numerical values or sub-ranges encompassed within thatrange as if each numerical value and sub-range is explicitly recited. Asan illustration, a numerical range of “about 1 to about 5” should beinterpreted to include not only the explicitly recited values of about 1to about 5, but also include individual values and sub-ranges within theindicated range. Thus, included in this numerical range are individualvalues such as 2, 3, and 4 and sub-ranges such as from 1-2, from 1-3,from 1-4, from 2-3, from 2-4, from 2-5, from 3-4, and from 3-5, etc., aswell as 1, 2, 3, 4, and 5, individually.

This same principle applies to ranges reciting only one numerical valueas a minimum or a maximum. Furthermore, such an interpretation shouldapply regardless of the breadth of the range or the characteristicsbeing described.

Reference in this application may be made to compositions, systems, ormethods that provide “improved” or “enhanced” performance. It is to beunderstood that unless otherwise stated, such “improvement” or“enhancement” is a measure of a benefit obtained based on a comparisonto compositions, systems or methods in the prior art. Furthermore, it isto be understood that the degree of improved or enhanced performance mayvary between disclosed embodiments and that no equality or consistencyin the amount, degree, or realization of improvement or enhancement isto be assumed as universally applicable.

Reference throughout this specification to “an example” means that aparticular feature, structure, or characteristic described in connectionwith the example is included in at least one embodiment. Thus,appearances of the phrases “in an example” in various places throughoutthis specification are not necessarily all referring to the sameembodiment.

It is noted that testosterone levels can be monitored via a variety oftestosterone assays. Such testosterone assays (e.g., for serumtestosterone, total testosterone, free testosterone etc.) can beperformed as part of a diagnosis of hypogonadism, a treatment efficacyassessment, or discontinuation of therapy. The assays themselves can beradioimmunoassays via commercial kits, validated mass spectrometricmethods, or any other suitable assay.

It is also noted that typical regulatory approval targets for TT arebased on responder outcomes targeted for patients on TT such thataverage daily T levels (C_(avg)) are restored in the normal eugonadalrange in at least 75% of the treated patients and no more than 15% ofthe patients experience maximum serum T concentrations (C_(max))>1500ng/dL. Unacceptably high serum T level is typically defined as maximumserum concentrations of >1800 ng/dL observed in a patient post dosing inthe dosing interval is typically assessed by % of patients in a groupthat shows C_(max)>1800 ng/dL.

Described herein, in one embodiment, is a method of restoringtestosterone levels in a patient needing testosterone therapy (TT). Themethod can include administering a therapeutically effective amount of atestosterone ester, such as testosterone tridecanoate (TU), to thepatient via an oral dosage form. The oral dosage form can beadministered to the patient in a fixed dose dosing regimen. It is notedthat for the sake of clarity and brevity, T13 is generally referred toin this disclosure as an example testosterone ester. These references toT13 are not intended to be particularly limiting unless otherwisespecified. More broadly, references to T13 can generally refer to anysuitable testosterone ester.

Described herein, in one embodiment, is a method of restoring adihydrotestosterone (DHT) to testosterone (T) ratio (DHT/T) to a normalrange (e.g. 0.05-0.33) in patients needing TT. The method can includeadministering a therapeutically effective amount of a testosteroneester, such as T13, to a patient via an oral dosage form using a fixeddose dosing regimen. In one aspect, the fixed dose dosing regimen caninclude a single daily dose of a therapeutically effective amount of T13to an individual in need of treatment. In another aspect, the fixed dosedosing regimen can include oral administration of a therapeuticallyeffective amount of T13 once or twice per day. In one aspect, the methodcomprises oral administration of a therapeutically effective amount ofT13 twice per day with food or fat containing food. In one aspect, themethod comprises oral administration of T13 in a single fixed dosedosing regimen which provides from about 750 mg to 1150 mg of T13 perday. In one aspect, the method comprises oral administration of T13 in asingle fixed dose dosing regimen which provides from about 750 mg to1100 mg of T13 per day. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 375 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 400 mg to 525 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides about 500 mg T13administered twice daily (e.g., about 1000 mg T13 total daily dose). Inone aspect, the method comprises oral administration of T13 in a fixeddose dosing regimen which provides about 900-1100 mg T13 administeredonce daily (e.g., about 1000 mg T13 total daily dose administered once aday).

Described herein, in one embodiment, is a method that can provide safeand effective testosterone therapy in patients needing TT with aT13-containing oral dosage form using a fixed dose dosing regimen. Inone aspect, the method comprises oral administration of therapeuticallyeffective amount of T13 to a patient in need of treatment via a singlefixed dose dosing regimen. In one aspect, the method comprises oraladministration of T13 twice per day in a fixed dose dosing regimen. Inone aspect, the method comprises oral administration of atherapeutically effective amount of T13 once or twice per day with food.In one aspect, the method comprises oral administration of atherapeutically effective amount of T13 once or twice per day with fatcontaining food. In one aspect, the method comprises oral administrationof T13 in a single fixed dose dosing regimen which provides from about750 mg to 1150 mg of T13 per day. In one aspect, the method comprisesoral administration of T13 in a single fixed dose dosing regimen whichprovides from about 800 mg to 1100 mg of T13 per day. In one aspect, themethod comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 400 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides from about 900 mg to1100 mg of T13 administered once daily. In one aspect, the methodcomprises oral administration of T13 in a fixed dose dosing regimenwhich provides about 500 mg T13 administered twice daily (e.g., about1000 mg T13 total daily dose). In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen of T13 whichprovides about 900-1100 mg T13 administered once daily (e.g., about 1000mg T13 total daily dose).

Described herein, in one embodiment, is a method of restoring averagetestosterone levels to a normal eugonadal range in patients needing TT.The method can include administering a therapeutically effective amountof a testosterone ester to a patient via an oral dosage form using afixed dose dosing regimen. In one aspect, the method comprises oraladministration of a therapeutically effective amount of T13 to a patientin need of treatment via a single fixed dose dosing regimen. In oneaspect, the method comprises oral administration of a therapeuticallyeffective amount of T13 once or twice per day in a fixed dose dosingregimen of T13. In one aspect, the method comprises oral administrationof a therapeutically effective amount of T13 once or twice per day withfood or fat containing food. In one aspect, the method comprises oraladministration of T13 in a single fixed dose dosing regimen whichprovides from about 750 mg to 1150 mg of T13 per day. In one aspect, themethod comprises oral administration of T13 in a single fixed dosedosing regimen which provides from about 800 mg to 1100 mg of T13 perday. In one aspect, the method comprises oral administration of T13 in afixed dose dosing regimen which provides from about 400 mg to 550 mg ofT13 administered twice daily. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 450 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides about 500 mg T13 administered twice daily (e.g.,about 1000 mg T13 total daily dose). In one aspect, the method comprisesoral administration of T13 in a fixed dose dosing regimen which providesabout 900-1100 mg T13 administered once daily (e.g., about 1000 mg T13total daily dose administered once a day).

Described herein, in one embodiment, is a method of restoring averagetestosterone levels to a normal eugonadal range while avoidingunacceptably high serum testosterone levels in patients needing TT. Themethod can include administering a therapeutically effective amount of atestosterone ester to a patient via an oral dosage form using a fixeddose dosing regimen. In one aspect, the method comprises oraladministration of a therapeutically effective amount of T13 to a patientin need of treatment via a single fixed dose dosing regimen. In oneaspect, the method comprises oral administration of a therapeuticallyeffective amount of T13 once or twice per day in a fixed dose dosingregimen of T13. In one aspect, the method comprises oral administrationof a therapeutically effective amount of T13 once or twice per day withfood or fat containing food. In one aspect, the method comprises oraladministration of T13 in a single fixed dose dosing regimen whichprovides from about 750 mg to 1150 mg of T13 per day. In one aspect, themethod comprises oral administration of T13 in a single fixed dosedosing regimen which provides from about 800 mg to 1100 mg of T13 perday. In one aspect, the method comprises oral administration of T13 in afixed dose dosing regimen which provides from about 400 mg to 550 mg ofT13 administered twice daily. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 450 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides about 500 mg T13 administered twice daily (e.g.,about 1000 mg T13 total daily dose). In one aspect, the method comprisesoral administration of T13 in a fixed dose dosing regimen which providesabout 900-1100 mg T13 administered once daily (e.g., about 1000 mg T13total daily dose administered once a day).

Described herein, in one embodiment, is a method of restoring averagetestosterone levels to a normal eugonadal range while avoidingunacceptably high testosterone levels (e.g. maximum testosteroneconcentration post administration>1500 ng/dL) in patients needing TT.The method can include administering a therapeutically effective amountof a testosterone ester to a patient via an oral dosage form using afixed dose dosing regimen. In one aspect, the method comprises oraladministration of a therapeutically effective amount of T13 to a patientin need of treatment via a single fixed dose dosing. In one aspect, themethod comprises oral administration of a therapeutically effectiveamount of T13 once or twice per day in a fixed dose dosing regimen ofT13. In one aspect, the method comprises oral administration of atherapeutically effective amount of T13 once or twice per day with foodor fat containing food. In one aspect, the method comprises oraladministration of T13 in a single fixed dose dosing regimen whichprovides from about 750 mg to 1150 mg of T13 per day. In one aspect, themethod comprises oral administration of T13 in a single fixed dosedosing regimen which provides from about 800 mg to 1100 mg of T13 perday. In one aspect, the method comprises oral administration of T13 in afixed dose dosing regimen which provides from about 400 mg to 550 mg ofT13 administered twice daily. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 450 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides about 500 mg T13 administered twice daily (e.g.,about 1000 mg T13 total daily dose). In one aspect, the method comprisesoral administration of T13 in a fixed dose dosing regimen which providesabout 900-1100 mg T13 administered once daily (e.g., about 1000 mg T13total daily dose administered once a day).

In one aspect of these embodiments, ≤20% of the treated patients (e.g.,in a population of patients or subjects where the population is 10 ormore, 20 or more, 30 or more, 40 or more, 50 or more, 60 or more, 70 ormore, 80 or more, 90 or more, or 100 or more patients or subjects) haveunacceptably high testosterone levels (e.g., maximum serum testosteroneconcentration post administration>1500 ng/dL) when treated with an oraldosage form including a therapeutically effective amount of T13 via afixed dose dosing regimen that does not need dose adjustment ortitration and that provides ≤1150 mg of T13 per day. In one aspect, themethod comprises oral administration of a therapeutically effectiveamount of T13 to a patient in need of treatment via a fixed dose dosingregimen. In one aspect, the method comprises oral administration of atherapeutically effective amount of T13 once or twice per day in a fixeddose dosing regimen of T13. In one aspect, the method comprises oraladministration of a therapeutically effective amount of T13 once ortwice per day with food or fat containing food. In one aspect, themethod comprises oral administration of T13 in a single fixed dosedosing regimen which provides from about 750 mg to 1150 mg of T13 perday. In one aspect, the method comprises oral administration of T13 in asingle fixed dose dosing regimen which provides from about 800 mg to1100 mg of T13 per day. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 400 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 450 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides about 500 mg T13administered twice daily (e.g., about 1000 mg T13 total daily dose). Inone aspect, the method comprises oral administration of T13 in a fixeddose dosing regimen which provides about 900-1100 mg T13 administeredonce daily (e.g., about 1000 mg T13 total daily dose administered once aday).

In one aspect of these embodiments, ≤15% of the treated patients (e.g.,in a population of patients or subjects where the populations is 10 ormore, 20 or more, 30 or more, 40 or more, 50 or more, 60 or more, 70 ormore, 80 or more, 90 or more or 100 or more patients or subjects)experience maximum testosterone concentration post administration>1500ng/dL when treated with an oral dosage form including a therapeuticallyeffective amount of T13 to a patient via a fixed dose dosing regimenthat does not need dose adjustment or titration and that provides≤1150mg daily dose of T13. In one aspect, the method comprises oraladministration of a therapeutically effective amount of T13 to a patientin need of treatment via a fixed dose dosing regimen. In one aspect, themethod comprises oral administration of a therapeutically effectiveamount of T13 once or twice per day in a fixed dose dosing regimen ofT13. In one aspect, the method comprises oral administration of atherapeutically effective amount of T13 once or twice per day with foodor fat containing food. In one aspect, the method comprises oraladministration of T13 in a single fixed dose dosing regimen whichprovides from about 750 mg to 1150 mg of T13 per day. In one aspect, themethod comprises oral administration of T13 in a single fixed dosedosing regimen which provides from about 800 mg to 1100 mg of T13 perday. In one aspect, the method comprises oral administration of T13 in afixed dose dosing regimen which provides from about 400 mg to 550 mg ofT13 administered twice daily. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 450 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides about 500 mg T13 administered twice daily (e.g.,about 1000 mg T13 total daily dose). In one aspect, the method comprisesoral administration of T13 in a fixed dose dosing regimen which providesabout 900-1100 mg T13 administered once daily (e.g., about 1000 mg T13total daily dose administered once a day).

Described herein, in one embodiment, is a method of restoringtestosterone levels to a normal eugonadal range while avoidingunacceptably high testosterone levels (e.g., maximum serum testosteroneconcentration post administration>1800 ng/dL) in ≥90% of patients (e.g.,in a population of patients or subjects where the populations is 10 ormore, 20 or more, 30 or more, 40 or more, 50 or more, 60 or more, 70 ormore, 80 or more, 90 or more or 100 or more patients or subjects)needing TT. The method can include administering a therapeuticallyeffective amount of a testosterone ester to a patient via an oral dosageform using a fixed dose dosing regimen. In one aspect, the methodcomprises oral administration of a therapeutically effective amount ofT13 to a patient in need of treatment via a single fixed dose dosingregimen. In one aspect, the method comprises oral administration of atherapeutically effective amount of T13 once or twice per day in a fixeddose dosing regimen of T13. In one aspect, the method comprises oraladministration of a therapeutically effective amount of T13 once ortwice per day with food or fat containing food. In one aspect, themethod comprises oral administration of T13 in a single fixed dosedosing regimen which provides from about 750 mg to 1150 mg of T13 perday. In one aspect, the method comprises oral administration of T13 in asingle fixed dose dosing regimen which provides from about 800 mg to1100 mg of T13 per day. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 400 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 450 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides about 500 mg T13administered twice daily (e.g., about 1000 mg T13 total daily dose). Inone aspect, the method comprises oral administration of T13 in a fixeddose dosing regimen which provides about 900-1100 mg T13 administeredonce daily (e.g., about 1000 mg T13 total daily dose administered once aday).

Described herein, in one embodiment, is a method of restoringtestosterone levels to a normal eugonadal range while avoidingunacceptably high serum testosterone levels, (e.g., maximum serumtestosterone concentration post administration>1800 ng/dL) in ≥95%patients (e.g., in a population of patients or subjects where thepopulations is 10 or more, 20 or more, 30 or more, 40 or more, 50 ormore, 60 or more, 70 or more, 80 or more, 90 or more or 100 or morepatients or subjects) needing TT. The method can include administering atherapeutically effective amount of a testosterone ester to a patientvia an oral dosage form using a fixed dose dosing regimen. In oneaspect, the method comprises oral administration of a therapeuticallyeffective amount of T13 to a patient in need of treatment via a singlefixed dose dosing regimen. In one aspect, the method comprises oraladministration of a therapeutically effective amount of T13 once ortwice per day in a fixed dose dosing regimen of T13. In one aspect, themethod comprises oral administration of a therapeutically effectiveamount of T13 once or twice per day with food or fat containing food. Inone aspect, the method comprises oral administration of T13 in a singlefixed dose dosing regimen which provides from about 750 mg to 1150 mg ofT13 per day. In one aspect, the method comprises oral administration ofT13 in a single fixed dose dosing regimen which provides from about 800mg to 1100 mg of T13 per day. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 400 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 450 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides about 500 mg T13administered twice daily (e.g., about 1000 mg T13 total daily dose). Inone aspect, the method comprises oral administration of T13 in a fixeddose dosing regimen which provides about 900-1100 mg T13 administeredonce daily (e.g., about 1000 mg T13 total daily dose administered once aday).

Described herein, in one embodiment, is a method of restoringtestosterone levels to a normal eugonadal range while avoidingunacceptably high serum testosterone levels (e.g., maximum serumtestosterone concentration post administration>2500 ng/dL) in patientsneeding TT. The method can include administering a therapeuticallyeffective amount of a testosterone ester to a patient via an oral dosageform using a fixed dose dosing regimen. In one aspect, the methodcomprises oral administration of a therapeutically effective amount ofT13 to a patient in need of treatment via a single fixed dose dosingregimen of T13. In one aspect, the method comprises oral administrationof a therapeutically effective amount of T13 once or twice per day in afixed dose dosing regimen of T13. In one aspect, the method comprisesoral administration of a therapeutically effective amount of T13 once ortwice per day with food or fat containing food. In one aspect, themethod comprises oral administration of T13 in a single fixed dosedosing regimen which provides from about 750 mg to 1150 mg of T13 perday. In one aspect, the method comprises oral administration of T13 in asingle fixed dose dosing regimen which provides from about 800 mg to1100 mg of T13 per day. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 400 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 450 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides about 500 mg T13administered twice daily (e.g., about 1000 mg T13 total daily dose). Inone aspect, the method comprises oral administration of T13 in a fixeddose dosing regimen which provides about 900-1100 mg T13 administeredonce daily (e.g., about 1000 mg T13 total daily dose administered once aday).

Described herein, in one embodiment, is a method of restoringtestosterone levels to a normal eugonadal range while avoidingunacceptably high serum testosterone levels (e.g., maximum serumtestosterone concentration post administration>2500 ng/dl) in ≥98%patients (e.g., in a population of patients or subjects where thepopulations is 10 or more, 20 or more, 30 or more, 40 or more, 50 ormore, 60 or more, 70 or more, 80 or more, 90 or more or 100 or morepatients or subjects) needing TT. The method can include administering atherapeutically effective amount of a testosterone ester to a patientvia an oral dosage form using a fixed dose dosing regimen. In oneaspect, the method comprises oral administration of a therapeuticallyeffective amount of T13 to a patient in need of treatment via a singlefixed dose dosing regimen of T13. In one aspect, the method comprisesoral administration of a therapeutically effective amount of T13 once ortwice per day in a fixed dose dosing regimen of T13. In one aspect, themethod comprises oral administration of a therapeutically effectiveamount of T13 once or twice per day with food or fat containing food. Inone aspect, the method comprises oral administration of T13 in a singlefixed dose dosing regimen which provides from about 750 mg to 1150 mg ofT13 per day. In one aspect, the method comprises oral administration ofT13 in a single fixed dose dosing regimen which provides from about 800mg to 1100 mg of T13 per day. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 400 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 450 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides about 500 mg T13administered twice daily (e.g., about 1000 mg T13 total daily dose). Inone aspect, the method comprises oral administration of T13 in a fixeddose dosing regimen which provides about 900-1100 mg T13 administeredonce daily (e.g., about 1000 mg T13 total daily dose administered once aday).

Described herein, in one embodiment, is a method of restoringtestosterone levels to a normal eugonadal range while avoidingunacceptably high serum testosterone levels (e.g., maximum serumtestosterone concentration post administration>2500 ng/dl) in allpatients (e.g., in a population of patients or subjects where thepopulations is 10 or more, 20 or more, 30 or more, 40 or more, 50 ormore, 60 or more, 70 or more, 80 or more, 90 or more or 100 or morepatients or subjects) needing TT. The method can include administering atherapeutically effective amount of a testosterone ester to a patientvia an oral dosage form using a fixed dose dosing regimen. In oneaspect, the method comprises oral administration of a therapeuticallyeffective amount of T13 to a patient in need of treatment via a fixeddose dosing regimen. In one aspect, the method comprises oraladministration of a therapeutically effective amount of T13 once ortwice per day in a fixed dose dosing regimen of T13. In one aspect, themethod comprises oral administration of a therapeutically effectiveamount of T13 once or twice per day with food or fat containing food. Inone aspect, the method comprises oral administration of T13 in a singlefixed dose dosing regimen which provides from about 750 mg to 1150 mg ofT13 per day. In one aspect, the method comprises oral administration ofT13 in a single fixed dose dosing regimen which provides from about 800mg to 1100 mg of T13 per day. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 400 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 450 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides about 500 mg T13administered twice daily (e.g., about 1000 mg T13 total daily dose). Inone aspect, the method comprises oral administration of T13 in a fixeddose dosing regimen which provides about 900-1100 mg T13 administeredonce daily (e.g., about 1000 mg T13 total daily dose administered once aday).

Described herein, in one embodiment, is a method of restoringtestosterone levels in patients needing TT with an oral dosage formadministered in a dosing regimen that does not need dose adjustment ortitration and that provides at least a 750 mg of T13 per day. In oneaspect, the method comprises oral administration of a therapeuticallyeffective amount of T13 to a patient in need of treatment via a fixeddose dosing regimen. In one aspect, the method comprises oraladministration of a therapeutically effective amount of T13 once ortwice per day in a fixed dose dosing regimen of T13. In one aspect, themethod comprises oral administration of a therapeutically effectiveamount of T13 twice per day with food or fat containing food. In oneaspect, the method comprises oral administration of T13 in a singlefixed dose dosing regimen which provides from about 750 mg to 1150 mg ofT13 per day. In one aspect, the method comprises oral administration ofT13 in a single fixed dose dosing regimen which provides from about 800mg to 1100 mg of T13 per day. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 400 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 450 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides about 500 mg T13administered twice daily (e.g., about 1000 mg T13 total daily dose). Inone aspect, the method comprises oral administration of T13 in a fixeddose dosing regimen which provides about 900-1100 mg T13 administeredonce daily (e.g., about 1000 mg T13 total daily dose administered once aday).

Described herein, in one embodiment, is a method of restoring C_(avg)testosterone levels to a normal range by administering T13 in an oraldosage form using a dosing regimen that does not need dose adjustment ortitration and that provides at least a daily dose of 750 mg of T13 perday and wherein at least 75% of the patients (e.g., in a population ofpatients or subjects where the populations is 10 or more, 20 or more, 30or more, 40 or more, 50 or more, 60 or more, 70 or more, 80 or more, 90or more or 100 or more patients or subjects) treated using the dosingregimen described herein achieve C_(avg) testosterone levels within thenormal range. In one aspect, the method comprises oral administration ofa therapeutically effective amount of T13 to a patient in need oftreatment via a fixed dose dosing regimen. In one aspect, the methodcomprises oral administration of a therapeutically effective amount ofT13 once or twice per day in a fixed dose dosing regimen of T13. In oneaspect, the method comprises oral administration of a therapeuticallyeffective amount of T13 once or twice per day with food or fatcontaining food. In one aspect, the method comprises oral administrationof T13 in a single fixed dose dosing regimen which provides from about750 mg to 1150 mg of T13 per day. In one aspect, the method comprisesoral administration of T13 in a single fixed dose dosing regimen whichprovides from about 800 mg to 1100 mg of T13 per day. In one aspect, themethod comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 400 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides from about 450 mg to550 mg of T13 administered twice daily. In one aspect, the methodcomprises oral administration of T13 in a fixed dose dosing regimenwhich provides about 500 mg T13 administered twice daily (e.g., about1000 mg T13 total daily dose). In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which providesabout 900-1100 mg T13 administered once daily (e.g., about 1000 mg T13total daily dose administered once a day).

Described herein, in one embodiment, is a method of restoring C_(avg)testosterone levels to a normal range by administering T13 in an oraldosage form using a dosing regimen that does not need dose adjustment ortitration and that provides at least a daily dose of 800 mg of T13 perday and wherein at least 75% of the patients (e.g., in a population ofpatients or subjects where the populations is 10 or more, 20 or more, 30or more, 40 or more, 50 or more, 60 or more, 70 or more, 80 or more, 90or more or 100 or more patients or subjects) treated using the dosingregimen described herein achieve C_(avg) testosterone levels within thenormal range. In one aspect, the method comprises oral administration ofa therapeutically effective amount of T13 to a patient in need oftreatment via a fixed dose dosing regimen. In one aspect, the methodcomprises oral administration of a therapeutically effective amount ofT13 once or twice per day in a fixed dose dosing regimen of T13. In oneaspect, the method comprises oral administration of a therapeuticallyeffective amount of T13 once or twice per day with food or fatcontaining food. In one aspect, the method comprises oral administrationof T13 in a single fixed dose dosing regimen which provides from about750 mg to 1150 mg of T13 per day. In one aspect, the method comprisesoral administration of T13 in a single fixed dose dosing regimen whichprovides from about 800 mg to 1100 mg of T13 per day. In one aspect, themethod comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 400 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides from about 450 mg to550 mg of T13 administered twice daily. In one aspect, the methodcomprises oral administration of T13 in a fixed dose dosing regimenwhich provides about 500 mg T13 administered twice daily (e.g., about1000 mg T13 total daily dose). In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which providesabout 900-1100 mg T13 administered once daily (e.g., about 1000 mg T13total daily dose administered once a day).

Described herein, in one embodiment, is a method of restoring C_(avg)testosterone levels to a normal range by administering T13 in an oraldosage form using a dosing regimen that does not need dose adjustment ortitration and that provides at least a 850 mg of T13 per day and whereinat least 75% of the patients (e.g., in a population of patients orsubjects where the populations is 10 or more, 20 or more, 30 or more, 40or more, 50 or more, 60 or more, 70 or more, 80 or more, 90 or more or100 or more patients or subjects) treated using the dosing regimendescribed herein achieve C_(avg) testosterone levels within the normalrange. In one aspect, the method comprises oral administration of atherapeutically effective amount of T13 to a patient in need oftreatment via a fixed dose dosing regimen. In one aspect, the methodcomprises oral administration of a therapeutically effective amount ofT13 once or twice per day in a fixed dose dosing regimen of T13. In oneaspect, the method comprises oral administration of a therapeuticallyeffective amount of T13 once or twice per day with food or fatcontaining food. In one aspect, the method comprises oral administrationof T13 in a single fixed dose dosing regimen which provides from about750 mg to 1150 mg of T13 per day. In one aspect, the method comprisesoral administration of T13 in a single fixed dose dosing regimen whichprovides from about 800 mg to 1100 mg of T13 per day. In one aspect, themethod comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 400 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides from about 450 mg to550 mg of T13 administered twice daily. In one aspect, the methodcomprises oral administration of T13 in a fixed dose dosing regimenwhich provides about 500 mg T13 administered twice daily (e.g., about1000 mg T13 total daily dose). In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which providesabout 900-1100 mg T13 administered once daily (e.g., about 1000 mg T13total daily dose administered once a day).

Described herein, in one embodiment, is a method of restoring C_(avg)testosterone levels to a normal range by administering T13 in an oraldosage form using a dosing regimen that does not need dose adjustment ortitration and that provides at least a daily dose of 900 mg of T13 perday and wherein at least 75% of the patients (e.g., in a population ofpatients or subjects where the populations is 10 or more, 20 or more, 30or more, 40 or more, 50 or more, 60 or more, 70 or more, 80 or more, 90or more or 100 or more patients or subjects) treated using the dosingregimen described herein achieve C_(avg) testosterone levels within thenormal range. In one aspect, the method comprises oral administration ofa therapeutically effective amount of T13 to a patient in need oftreatment via a fixed dose dosing regimen. In one aspect, the methodcomprises oral administration of a therapeutically effective amount ofT13 once or twice per day in a fixed dose dosing regimen of T13. In oneaspect, the method comprises oral administration of a therapeuticallyeffective amount of T13 once or twice per day with food or fatcontaining food. In one aspect, the method comprises oral administrationof T13 in a single fixed dose dosing regimen which provides from about750 mg to 1150 mg of T13 per day. In one aspect, the method comprisesoral administration of T13 in a single fixed dose dosing regimen whichprovides from about 800 mg to 1100 mg of T13 per day. In one aspect, themethod comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 400 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides from about 450 mg to550 mg of T13 administered twice daily. In one aspect, the methodcomprises oral administration of T13 in a fixed dose dosing regimenwhich provides about 500 mg T13 administered twice daily (e.g., about1000 mg T13 total daily dose). In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which providesabout 900-1100 mg T13 administered once daily (e.g., about 1000 mg T13total daily dose administered once a day).

Described herein, in one embodiment, is a method of restoring C_(avg)testosterone levels to a normal range by administering T13 in an oraldosage form using a dosing regimen that does not need dose adjustment ortitration and that provides at least a daily dose of 950 mg of T13 perday and wherein at least 75% of the patients (e.g., in a population ofpatients or subjects where the populations is 10 or more, 20 or more, 30or more, 40 or more, 50 or more, 60 or more, 70 or more, 80 or more, 90or more or 100 or more patients or subjects) treated using the dosingregimen described herein achieve C_(avg) testosterone levels within thenormal range. In one aspect, the method comprises oral administration ofa therapeutically effective amount of T13 to a patient in need oftreatment via a fixed dose dosing regimen. In one aspect, the methodcomprises oral administration of a therapeutically effective amount ofT13 once or twice per day in a fixed dose dosing regimen of T13. In oneaspect, the method comprises oral administration of a therapeuticallyeffective amount of T13 once or twice per day with food or fatcontaining food. In one aspect, the method comprises oral administrationof T13 in a single fixed dose dosing regimen which provides from about750 mg to 1150 mg of T13 per day. In one aspect, the method comprisesoral administration of T13 in a single fixed dose dosing regimen whichprovides from about 800 mg to 1100 mg of T13 per day. In one aspect, themethod comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 400 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides from about 450 mg to550 mg of T13 administered twice daily. In one aspect, the methodcomprises oral administration of T13 in a fixed dose dosing regimenwhich provides about 500 mg T13 administered twice daily (e.g., about1000 mg T13 total daily dose). In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which providesabout 900-1100 mg T13 administered once daily (e.g., about 1000 mg T13total daily dose administered once a day).

Described herein, in one embodiment, is a method of restoring C_(avg)testosterone levels to a normal range by administering T13 in an oraldosage form using a dosing regimen that does not need dose adjustment ortitration and that provides at least a daily dose of 975 mg of T13 perday and wherein at least 75% of the patients (e.g., in a population ofpatients or subjects where the populations is 10 or more, 20 or more, 30or more, 40 or more, 50 or more, 60 or more, 70 or more, 80 or more, 90or more or 100 or more patients or subjects) treated using the dosingregimen described herein achieve C_(avg) testosterone levels within thenormal range. In one aspect, the method comprises oral administration ofa therapeutically effective amount of T13 to a patient in need oftreatment via a fixed dose dosing regimen. In one aspect, the methodcomprises oral administration of a therapeutically effective amount ofT13 once or twice per day in a fixed dose dosing regimen of T13. In oneaspect, the method comprises oral administration of a therapeuticallyeffective amount of T13 once or twice per day with food or fatcontaining food. In one aspect, the method comprises oral administrationof T13 in a single fixed dose dosing regimen which provides from about750 mg to 1150 mg of T13 per day. In one aspect, the method comprisesoral administration of T13 in a single fixed dose dosing regimen whichprovides from about 800 mg to 1100 mg of T13 per day. In one aspect, themethod comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 400 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides from about 450 mg to550 mg of T13 administered twice daily. In one aspect, the methodcomprises oral administration of T13 in a fixed dose dosing regimenwhich provides about 500 mg T13 administered twice daily (e.g., about1000 mg T13 total daily dose). In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which providesabout 900-1100 mg T13 administered once daily (e.g., about 1000 mg T13total daily dose administered once a day).

Described herein, in one embodiment, is a method of restoring C_(avg)testosterone levels to a normal range by administering T13 in an oraldosage form using a dosing regimen that does not need dose adjustment ortitration and that provides at least a 980 mg of T13 per day and whereinat least 75% of the patients (e.g., in a population of patients orsubjects where the populations is 10 or more, 20 or more, 30 or more, 40or more, 50 or more, 60 or more, 70 or more, 80 or more, 90 or more or100 or more patients or subjects) treated using the dosing regimendescribed herein achieve C_(avg) testosterone levels within the normalrange. In one aspect, the method comprises oral administration of atherapeutically effective amount of T13 to a patient in need oftreatment via a fixed dose dosing regimen. In one aspect, the methodcomprises oral administration of a therapeutically effective amount ofT13 once or twice per day in a single fixed dose dosing regimen. In oneaspect, the method comprises oral administration of a therapeuticallyeffective amount of T13 once or twice per day in a fixed dose dosingregimen of T13. In one aspect, the method comprises oral administrationof a therapeutically effective amount of T13 once or twice per day withfood or fat containing food. In one aspect, the method comprises oraladministration of T13 in a single fixed dose dosing regimen whichprovides from about 750 mg to 1150 mg of T13 per day. In one aspect, themethod comprises oral administration of T13 in a single fixed dosedosing regimen which provides from about 800 mg to 1100 mg of T13 perday. In one aspect, the method comprises oral administration of T13 in afixed dose dosing regimen which provides from about 400 mg to 550 mg ofT13 administered twice daily. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 450 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides about 500 mg T13 administered twice daily (e.g.,about 1000 mg T13 total daily dose). In one aspect, the method comprisesoral administration of T13 in a fixed dose dosing regimen which providesabout 900-1100 mg T13 administered once daily (e.g., about 1000 mg T13total daily dose administered once a day).

Described herein, in one embodiment, is a method of restoring C_(avg)testosterone levels to a normal range by administering T13 in an oraldosage form using a dosing regimen that does not need dose adjustment ortitration and that provides at least a 990 mg of T13 per day and whereinat least 80% of the patients (e.g., in a population of patients orsubjects where the populations is 10 or more, 20 or more, 30 or more, 40or more, 50 or more, 60 or more, 70 or more, 80 or more, 90 or more or100 or more patients or subjects) treated using the dosing regimendescribed herein achieve C_(avg) testosterone levels within the normalrange. In one aspect, the method comprises oral administration of atherapeutically effective amount of TU to a patient in need of treatmentvia a fixed dose dosing regimen. In one aspect, the method comprisesoral administration of a therapeutically effective amount of T13 once ortwice per day in a fixed dose dosing regimen of T13. In one aspect, themethod comprises oral administration of a therapeutically effectiveamount of T13 once or twice per day with food or fat containing food. Inone aspect, the method comprises oral administration of T13 in a singlefixed dose dosing regimen which provides from about 750 mg to 1150 mg ofT13 per day. In one aspect, the method comprises oral administration ofT13 in a single fixed dose dosing regimen which provides from about 800mg to 1100 mg of T13 per day. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 400 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 450 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides about 500 mg T13administered twice daily (e.g., about 1000 mg T13 total daily dose). Inone aspect, the method comprises oral administration of T13 in a fixeddose dosing regimen which provides about 900-1100 mg T13 administeredonce daily (e.g., about 1000 mg T13 total daily dose administered once aday).

Described herein, in one embodiment, is a method of restoring C_(avg)testosterone levels to a normal range by administering T13 in an oraldosage form using a dosing regimen that does not need dose adjustment ortitration and that provides at least a 1000 mg of T13 per day andwherein at least 85% of the patients (e.g., in a population of patientsor subjects where the populations is 10 or more, 20 or more, 30 or more,40 or more, 50 or more, 60 or more, 70 or more, 80 or more, 90 or moreor 100 or more patients or subjects) treated using the dosing regimendescribed herein achieve C_(avg) testosterone levels within the normalrange. In one aspect, the method comprises oral administration of atherapeutically effective amount of UT to a patient in need of treatmentvia a fixed dose dosing regimen. In one aspect, the method comprisesoral administration of a therapeutically effective amount of T13 once ortwice per day in a fixed dose dosing regimen of T13. In one aspect, themethod comprises oral administration of a therapeutically effectiveamount of T13 once or twice per day with food or fat containing food. Inone aspect, the method comprises oral administration of T13 in a singlefixed dose dosing regimen which provides from about 750 mg to 1150 mg ofT13 per day. In one aspect, the method comprises oral administration ofT13 in a single fixed dose dosing regimen which provides from about 800mg to 1100 mg of T13 per day. In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which provides fromabout 400 mg to 550 mg of T13 administered twice daily. In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 450 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides about 500 mg T13administered twice daily (e.g., about 1000 mg T13 total daily dose). Inone aspect, the method comprises oral administration of T13 in a fixeddose dosing regimen which provides about 900-1100 mg T13 administeredonce daily (e.g., about 1000 mg T13 total daily dose administered once aday).

Described herein, in one embodiment, is a method of restoring C_(avg)testosterone levels to a normal range by administering T13 in an oraldosage form using a dosing regimen that does not need dose adjustment ortitration and that provides at least a 1050 mg of T13 per day andwherein at least 90% of the patients (e.g., in a population of patientsor subjects where the populations is 10 or more, 20 or more, 30 or more,40 or more, 50 or more, 60 or more, 70 or more, 80 or more, 90 or moreor 100 or more patients or subjects) treated using the dosing regimendescribed herein achieve C_(avg) testosterone levels within the normalrange. In one aspect, the method comprises oral administration of atherapeutically effective amount of T13 to a patient in need oftreatment via a fixed dose dosing regimen. In one aspect, the methodcomprises oral administration of a therapeutically effective amount ofT13 once or twice per day in a fixed dose dosing regimen of T13. In oneaspect, the method comprises oral administration of a therapeuticallyeffective amount of T13 twice per day with food or fat containing food.In one aspect, the method comprises oral administration of T13 in asingle fixed dose dosing regimen which provides from about 750 mg to1150 mg of T13 per day. In one aspect, the method comprises oraladministration of T13 in a single fixed dose dosing regimen whichprovides from about 800 mg to 1100 mg of T13 per day. In one aspect, themethod comprises oral administration of T13 in a fixed dose dosingregimen which provides from about 400 mg to 550 mg of T13 administeredtwice daily. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides from about 450 mg to550 mg of T13 administered twice daily. In one aspect, the methodcomprises oral administration of T13 in a fixed dose dosing regimenwhich provides about 500 mg T13 administered twice daily (e.g., about1000 mg T13 total daily dose). In one aspect, the method comprises oraladministration of T13 in a fixed dose dosing regimen which providesabout 900-1100 mg T13 administered once daily (e.g., about 1000 mg T13total daily dose administered once a day).

Described herein, in one embodiment, is a method of restoringtestosterone levels in a patient needing TT to within normal T levelswhile avoiding unacceptably high T levels. The method can includeadministering T13 via an oral dosage form using a dosing regimen thatdoes not need a dose adjustment or titration and that provides a dailyamount of T13 of from 750 mg to 1150 mg. In one aspect, the methodcomprises oral administration of a therapeutically effective amount ofUT to a patient in need of treatment via a fixed dose dosing regimen. Inone aspect, the method comprises oral administration of atherapeutically effective amount of T13 once or twice per day in a fixeddose dosing regimen of T13. In one aspect, the method comprises oraladministration of a therapeutically effective amount of T13 twice perday with food or fat containing food. In one aspect, the methodcomprises oral administration of T13 in a single fixed dose dosingregimen which provides from about 750 mg to 1150 mg of T13 per day. Inone aspect, the method comprises oral administration of T13 in a singlefixed dose dosing regimen which provides from about 800 mg to 1100 mg ofT13 per day. In one aspect, the method comprises oral administration ofT13 in a fixed dose dosing regimen which provides from about 400 mg to550 mg of T13 administered twice daily. In one aspect, the methodcomprises oral administration of T13 in a fixed dose dosing regimenwhich provides from about 450 mg to 550 mg of T13 administered twicedaily. In one aspect, the method comprises oral administration of T13 ina fixed dose dosing regimen which provides about 500 mg T13 administeredtwice daily (e.g., about 1000 mg T13 total daily dose). In one aspect,the method comprises oral administration of T13 in a fixed dose dosingregimen which provides about 900-1100 mg T13 administered once daily(e.g., about 1000 mg T13 total daily dose administered once a day).

Described herein, in one embodiment, is a method of restoringtestosterone levels in a patient needing TT to within normal T levelswhile avoiding unacceptably high T levels. The method can includeadministering T13 via an oral dosage form using a dosing regimen thatdoes not need a dose adjustment or titration and that provides a dailyamount of T13 of about 750-1150 mg.

Described herein, in one embodiment, is a method of restoringtestosterone levels in a patient needing TT to within normal T levelswhile avoiding unacceptably high T levels. The method can includeadministering T13 via an oral dosage form using a dosing regimen thatdoes not need a dose adjustment or titration and that provides a dailyamount of T13 of about 900-1100 mg.

Described herein, in one embodiment, is a method of restoringtestosterone levels in a patient needing TT to within normal T levelswhile avoiding unacceptably high T levels. The method can includeadministering T13 via an oral dosage form using a dosing regimen thatdoes not need a dose adjustment or titration and that provides a dailyamount of T13 of about 950-1100 mg.

Described herein, in one embodiment, is a method of restoringtestosterone levels in a patient needing TT to within normal T levelswhile avoiding unacceptably high T levels. The method can includeadministering T13 via an oral dosage form using a dosing regimen thatdoes not need a dose adjustment or titration and that provides a dailyamount of T13 of about 1000 mg.

Described herein, in one embodiment, is a method of restoringtestosterone levels in a patient needing TT to within normal T levelswhile avoiding unacceptably high T levels. The method can includeadministering T13 via an oral dosage form using a dosing regimen thatdoes not need a dose adjustment or titration and that provides a dailyamount of T13 of about 990-1010 mg.

Described herein, in one embodiment, is a method of restoringtestosterone levels in a patient needing TT to within normal T levelswhile avoiding unacceptably high T levels. The method can includeadministering T13 via an oral dosage form using a dosing regimen thatdoes not need a dose adjustment or titration and that provides a dailyamount of T13 of about 1000 mg.

In one embodiment, an unexpected finding of these studies, as outlinedin the Examples and described herein, is the surprising discovery that aTT dosing regimen including an appropriate single fixed oral dose of T13in the range from 750 mg to 1150 mg (or 950-1050 mg) can obviate theneed for a titration scheme or dose adjustment. This is unexpected sincerecent previous attempts to obtain regulatory approval of an oral T13based TT were based on dose titration schemes which were thought to beneeded to ensure adequate efficacy and safety of the therapy.Additionally, many marketed TTs require dose titrations or adjustment asindicated on the product's label.

While any oral dosage form can be utilized in the dosing regimen of thisinvention for TT, in some examples the dosage form can be a capsulecomprised of pharmaceutically acceptable components. In one embodiment,the dose of T13 is 375-575 mg (e.g., as 1 capsule or 2, 3, or 4 or morecapsules) administered orally two times daily for a total daily dose ofT13 from 750-150 mg. The oral dosage form can be administered with food(e.g., co-administered) having at least 10 g of fat, at least 15 g offat, at least 20 g of fat, or at least 30 g of fat, or an amount of fatwithin the range of 10-60 g.

The dosing regimen of this invention can include a daily dose of T13administered as a four times per day (QID), a thrice per day (TID), atwice per day (BID), or a once per day (QD) dosing. Whatever the numberof daily doses, each dose can be equally divided to provide a totaldaily dose of T13 between 750-1150 mg.

The oral testosterone replacement therapy described herein wasdiscovered to be safe and efficacious. For example, it is believed thatthe TT described herein meets (1), (2), (3), (4), and/or (5) of thefollowing criteria when used in a sufficient population of individualsneeding such therapy (e.g., hypogonadal men):

(1) Proportion of subjects with average serum T (C_(avg)) within thenormal range

(e.g., 300-1000 ng/dL): ≥75%, 77%, 79%, 81%, 83%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94% or 95% or more;

(2) Proportion of subjects with average serum T (C_(avg)) within thenormal range: ≥65%,

67%, 69%, 71%, 73%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84% or85% or more with a lower bound 95% CI (Confidence Interval);

Proportion with maximum serum T (C_(max)) outside the normal range:

(3) C_(max)>1500 ng/dL (no greater than 15%, 16%, 17%, 18%, 19% 20%,21%, 22%, 23%, 24% or 25%);

(4) C_(max) between 1800 and 2499 ng/dL (no greater than 5% 6%, 7%, 8%,9% or 10%); and

(5) C_(max)>2500 ng/dL (0%, or no greater than 1%, 2%, 3%, 4% or 5%).

In this context, a population of individuals typically refers to atleast 20 individuals (e.g., in need of treatment like hypogonadal males)and preferable at least 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80,85, 90, 95 or 100 individuals or more.

In some embodiments, testosterone concentrations (e.g., blood, serum, orplasma) can be checked periodically, e.g., 3-12 hours after the morningdose, starting as soon as one month or two weeks (or sooner) afterinitiating treatment with testosterone tridecanoate. When the totaltestosterone concentration consistently exceeds 1200, 1300, 1400, 1500,1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400 or 2500 ng/dL,therapy with testosterone tridecanoate can be discontinued as advised bytrained medical personnel. If the total testosterone concentration isconsistently below 300 ng/dL, an alternative treatment can be consideredas advised by trained medical personnel.

In another embodiment, testosterone (e.g., blood, serum, or plasma)concentrations can be checked periodically, e.g., any time between 3-12hours after the morning dose, starting as soon as one month afterinitiating treatment with testosterone tridecanoate. If the totaltestosterone concentration consistently exceeds 2500 ng/dL, therapy withtestosterone tridecanoate can be discontinued as advised by trainedmedical personnel. If the total testosterone concentration isconsistently below 300 ng/dL, an alternative treatment can be consideredas advised by trained medical personnel. As used in this paragraph,consistently can refer to two or more times or occurrences.

In yet another embodiment, increases in hematocrit levels, reflective ofincreases in red blood cell mass, may require discontinuation of oraltestosterone tridecanoate. Hematocrit levels can be checked prior toinitiating treatment. In some examples, it can be appropriate tore-evaluate the hematocrit levels starting from 3 months after startingtreatment, and then annually. In some cases, if hematocrit levels becomeelevated, the therapy can be discontinued until hematocrit levelsdecrease to an acceptable level.

Thus, in one embodiment, the dosing regimen comprises orallyadministering a dosage form of that comprises T13 and a carrierincluding a pharmaceutically acceptable additive. The pharmaceuticallyacceptable additives of this invention can include one or morelipophilic additives, one or more hydrophilic additives, other suitablepharmaceutically acceptable additives, or a combination thereof.

Thus, in some embodiments, orally administered testosterone tridecanoatecompositions can be used in the following exemplary replacementtherapies described below or previously in this specification.

In one example, a testosterone replacement therapy for a male patienthaving a condition associated with a deficiency or absence of endogenoustestosterone can include orally administering a fixed dose of atherapeutically effective amount of testosterone tridecanoate to thepatient with food.

In some examples, the fixed dose can be from 750 mg to 1150 mg T13 perday once a day (or twice a day as a divided dose (e.g., 375-575 mgadministered as a divided dose)).

In some examples, the fixed dose is 800-1100 mg testosteronetridecanoate per day (or twice a day as a divided dose (e.g., 400-550 mgadministered as a divided dose)).

In some examples, the fixed dose is 850-1050 mg testosteronetridecanoate per day (or twice a day as a divided dose (e.g., 425-525 mgadministered as a divided dose)).

In some examples, the fixed dose is 900-1100 mg testosteronetridecanoate per day (or twice a day as a divided dose (e.g., 450-550 mgadministered as a divided dose)).

In some examples, the fixed dose is 950-1050 mg testosteronetridecanoate per day (or twice a day as a divided dose (e.g., 475-525 mgadministered as a divided dose)).

In some examples, the fixed dose is 975-1025 mg testosteronetridecanoate per day (or twice a day as a divided dose (e.g.,487.5-512.5 mg administered as a divided dose)).

In some examples, the fixed dose is 990-1010 mg testosteronetridecanoate per day (or twice a day as a divided dose (e.g., 495-505 mgadministered as a divided dose)).

In some examples, the fixed dose is 995-1005 mg testosteronetridecanoate per day (or twice a day as a divided dose (e.g.,497.5-502.5 mg administered as a divided dose)).

In some examples, a serum testosterone level of said male is determinedafter initiation of therapy.

In some examples, a serum testosterone level of said male is determinedafter initiation of therapy wherein unacceptably high serum testosteronelevels after a fixed dose administration of testosterone tridecanoateindicates that the male discontinues said therapy.

In some examples, a serum testosterone level of said male is determinedafter initiation of therapy wherein unacceptably low serum testosteronelevels after a fixed dose administration of testosterone tridecanoateindicates that the male discontinues said therapy.

In some examples, the testosterone tridecanoate is formulated with alipophilic surfactant, a hydrophilic surfactant, or both.

In some examples, the testosterone tridecanoate is formulated with atriglyceride.

In some examples, the testosterone tridecanoate is formulated with afatty acid, a monoglyceride, a diglyceride, a triglyceride, ahydrophilic surfactant, a solidifying agent, or a combination thereof.

In some examples, the fixed dose is about 990 mg testosteronetridecanoate per day.

In some examples, the fixed dose is about 995 mg testosteronetridecanoate per day.

In some examples, the fixed dose is about 1000 mg testosteronetridecanoate per day.

In some examples, the fixed dose is about 1005 mg testosteronetridecanoate per day.

In some examples, the fixed dose is about 1010 mg testosteronetridecanoate per day.

In some examples, when the total serum testosterone concentrationconsistently exceeds 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900,2000, 2100, 2200, 2300, 2400 or 2500 ng/dL, therapy with testosteronetridecanoate is discontinued.

In some examples, when the total serum testosterone concentrationconsistently exceeds 2500 ng/dL, therapy with testosterone tridecanoateis discontinued.

In some examples, when the total serum testosterone concentrationconsistently exceeds 2100 ng/dL, therapy with testosterone tridecanoateis discontinued.

In some examples, when the total serum testosterone concentrationconsistently exceeds 1800 ng/dL, therapy with testosterone tridecanoateis discontinued.

In some examples, when the total serum testosterone concentrationconsistently exceeds 1500 ng/dL, therapy with testosterone tridecanoateis discontinued.

In some examples, when the total serum testosterone concentration isconsistently below 300 ng/dL, therapy with testosterone tridecanoate isdiscontinued.

In some examples, discontinuation criteria are assessed at steady state.

In some examples, discontinuation criteria are assessed at steady stateby measuring serum testosterone concentrations.

In some examples, discontinuation criteria are assessed at steady stateby measuring serum testosterone concentrations 1 to 12 hours after afixed dose administration of the oral testosterone tridecanoate.

In some examples, the therapy is discontinued when the subject'shematocrit or PSA levels are unacceptably high.

In some examples, the therapy meets 1, 2, 3, 4, or 5 of the followingcriteria when used in a sufficient population of individuals needingsuch therapy:

(1) Proportion of subjects with average serum T (C_(avg)) within thenormal range

(300-1000 ng/dL): >75%, 77%, 79%, 81%, 83%, 85%, 86%, 87%, 88%, 89%,90%, 91%, 92%, 93%, 94% or 95% or more;

(2) Proportion of subjects with average serum T (C_(avg)) within thenormal range: >65%,

67%, 69%, 71%, 73%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84% or85% or more with a lower bound 95% CI (Confidence Interval);

Proportion with maximum serum T (C_(max)) outside the normal range:

(3) C_(max)>1500 ng/dL (not >15%, 16%, 17%, 18%, 19% or 20%);

(4) C_(max) between 1800 and 2499 ng/dL (not >5% 6%, 7%, 8%, 9% or 10%);

(5) C_(max)>2500 ng/dL (none or not >1%, 2%, 3%, 4% or 5%);

wherein a population of individuals refers to typically at least 20individuals or at least 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80,85, 90, 95 or 100 individuals or more.

Thus, the testosterone replacement described herein, when used with apopulation of male subjects, provides safe and efficacious testosteronereplacement therapy.

Examples of T13 Compositions and Dosage Forms

The dosing regimens involving T13 compositions and dosage forms areexemplified below for oral TT. The compositions and dosage formsdescribed herein can be used with oral testosterone products andparticularly T13 that are suitable for oral administration. Any suitableoral unit dosage form can be used. For example, in some embodiments, theunit dosage form is a hard gelatin or soft gelatin capsule. In otherembodiments, the unit dosage form is a tablet or caplet. Other suitableunit dosage forms include, but are not limited to, powder, granulate,particulate, bead, pellet, sprinkle, suspension, solution, tablet,capsule, or combinations thereof. The dosing schemes or regimensdescribed herein can be used with oral testosterone products formulatedin any suitable manner.

Typical pharmaceutical compositions of this invention are

Composition 1 Composition 1 Ingredient Name % w/w mg/unit* TestosteroneTridecanoate 15-45 140-550 Pharmaceutical Acceptable Carriers 55-85550-950 Total 100.0  700-1500 *The unit quantity of each ingredient ofthe composition can be proportionally adjusted to the quantity for anysize or form of unit dosage form such as a capsule or a tablet.

Composition 2 Composition 2 Ingredient Name % w/w TestosteroneTridecanoate 15-45 Pharmaceutical Lipophilic Additives* 50-85 AcceptableCarriers Other Additives  0-40 Total 100.0 *Preferred LipophilicAdditives include one or more of mono-di glycerides, vegetable oils,fatty acid, triglycerides, phytosterols,Vitamin E, lecithin, omega 3fatty acids.

Composition 3 Composition 3 Ingredient Name % w/w TestosteroneTridecanoate 15-45 Pharmaceutical Hydrophilic Additives*  0-40Acceptable Carriers Other Additives 50-85 Total 100.0 *PreferredHydrophilic Additives include one or more of Cremophor RH 40, CremphorEL, Vitamin E TPGS, Tween 80, labrasol, etc.

Composition 4 Composition 4 Ingredient Name % w/w TestosteroneTridecanoate 15-45 Pharmaceutical Lipophilic Additives 50-85 AcceptableCarriers Hydrophilic Additives  0-40 Other Additives  0-20 Total 100.0

The compositions of dosage forms (e.g. capsule or tablet) describedherein can include a variety of pharmaceutically acceptable carriersknown in the art. Non-limited examples of the pharmaceutical acceptablecarriers include lipophilic additives, hydrophilic additives, otheradditives, and combinations thereof.

In one embodiment, the lipophilic additives include, but not limited to,lipidic solubilizers, lipophilic surfactants, and combinations thereof.The lipidic solubilizers can comprise at least about 50 wt % of thepharmaceutically acceptable carrier. Non-limiting examples of lipidicsolubilizers can include triglycerides, tocopherol, tocopherolderivatives, fatty acids, fatty acid glycerides, or combinationsthereof. The triglycerides can include hydrogenated soyabean oil,hydrogenated vegetable oil, corn oil, olive oil, soyabean oil, peanutoil, sesame oil, or combination thereof. In another embodiment, thefatty acids can include caprylic acid, capric acid, lauric acid,myristic acid, palmitic acid, stearic acid, richinoleic acid, arachidicacid, behenic acid, lignoceric acid, cerotic acid, myristoleic acid,palmitoleic acid, sapienic acid, oleic acid, elaidic acid, vaccenicacid, linoleic acid, γ-linoleic acid, linoeladic acid, arachidonic acid,erucic acid, or combination thereof. In an additional embodiment, thefatty acid glycerides can be monoglycerides, diglycerides, or mixturesthereof. Non-limiting examples of fatty acid glycerides that can be usedin the oral pharmaceutical compositions and dosage forms of the presentinvention include monoglycerides and/or diglycerides derived fromsources such as maize oil, poppy seed oil, safflower oil, sunflower oil,borage seed oil, peppermint oil, coconut oil, palm kernel oil, castoroil, or mixtures thereof. In one embodiment, the glyceride derivativesdescribed in the following surfactants may be used as lipidicsolubilizers as well.

In one embodiment, a surfactant is considered as a lipophilic surfactantwhen it has an HLB value of 10 or less. It is important to note thatsome lipophilic surfactants may also function as the lipidic solubilizercomponent of the compositions and oral dosage forms. Various lipophilicsurfactants can be used including, but not limited to mono-,di-glycerides of fatty acids like glyceryl monolinoleate (e.g. Maisine®35-1), mono- and di glycerides of caprylic, capric acid (e.g. Capmul®MCM), glyceryl monooleate, reaction mixtures of alcohols or polyalcoholswith a variety of natural and/or hydrogenated oils such as PEG-5hydrogenated castor oil, PEG-7 hydrogenated castor oil, PEG-9hydrogenated castor oil, PEG-6 corn oil (e.g. Labrafil® M 2125 CS),PEG-6 almond oil (e.g. Labrafil®M 1966 CS), PEG-6 apricot kernel oil(e.g. Labrafil®M 1944 CS), PEG-6 olive oil (e.g. Labrafil®M 1980 CS),PEG-6 peanut oil (e.g. Labrafil®M 1969 CS), PEG-6 hydrogenated palmkernel oil (e.g. Labrafil®. M 2130 BS), PEG-6 palm kernel oil (e.g.Labrafil® M 2130 CS), PEG-6 triolein (e.g. Labrafil® M 2735 CS), PEG-8corn oil (e.g. Labrafil® WL 2609 BS), PEG-20 corn glycerides (e.g.Crovol® M40), PEG-20 almond glycerides (e.g. Crovol® A40), lipophilicpolyoxyethylene-polyoxypropylene block co-polymers (e.g. Pluronic® L92,L101, L121 etc.); propylene glycol fatty acid esters, such as propyleneglycol monolaurate (e.g. Lauroglycol FCC), propylene glycol ricinoleate(e.g. Propymuls), propylene glycol monooleate (e.g. Myverol P-06),propylene glycol dicaprylate/dicaprate (e.g. Captex® 200), and propyleneglycol dioctanoate (e.g. Captex® 800), propylene glycol mono-caprylate(e.g. Capryol® 90); propylene glycol oleate (e.g. Lutrol OP2000);propylene glycol myristate; propylene glycol mono stearate; propyleneglycol hydroxy stearate; propylene glycol ricinoleate; propylene glycolisostearate; propylene glycol mono-oleate; propylene glycoldicaprylate/dicaprate; propylene glycol dioctanoate; propylene glycolcaprylate-caprate; propylene glycol dilaurate; propylene glycoldistearate; propylene glycol dicaprylate; propylene glycol dicaprate;mixtures of propylene glycol esters and glycerol esters such as mixturescomposed of the oleic acid esters of propylene glycol and glycerol (e.g.Arlacel® 186); sterol and sterol derivatives such as cholesterol,sitosterol, phytosterol, phytosterol fatty acid esters, PEG-5 soyasterol, PEG-10 soya sterol, PEG-20 soya sterol, and the like; glycerylpalmitostearate, glyceryl stearate, glyceryl distearate, glycerylmonostearate, or a combination thereof; sorbitan fatty acid esters suchas sorbitan monolaurate (e.g. Arlacel 20), sorbitan monopalmitate (e.g.Span-40), sorbitan monooleate (e.g. Span-80), sorbitan monostearate, andsorbitan tristearate, sorbitan monolaurate, sorbitan monopalmitate,sorbitan monooleate, sorbitan trioleate, sorbitan sesquioleate, sorbitantristearate, sorbitan monoisostearate, sorbitan sesquistearate, and thelike; fatty acids such as capric acid, caprylic acid, oleic acid,linoleic acid, myristic acid, menthol, menthol derivatives, lecithin,phosphatidyl choline, bile salts, cholesterol, sitosterol, phytosterol(e.g. GENEROL series from Henkel), PEG-5 soya sterol (e.g. Nikkol BPS-S,from Nikko), PEG-10 soya sterol (e.g. Nikkol BPS-10 from Nikko), PEG-20soya sterol (e.g. Nikkol BPS-20 from Nikko), and the like, and mixturesthereof.

In one embodiment, hydrophilic additives are selected from the groupconsisting of hydrophilic surfactant, celluloses—such as hydroxypropylcelluloses low molecular weight, low viscosity types (e.g. Methocel® E5,E6, E10 E15, LV100 etc. grades) and hydroxypropyl celluloses havinghigher molecular weight, medium to high viscosity (e.g. Methocel® K4M,K15M, K100M etc); polyvinylpyrrolidones (e.g. Kollidon k17, K30 etc);polyvinyl acetates and combinations thereof.

In further embodiment, a surfactant is considered as a hydrophilicsurfactant when it has an HLB value of greater than 10. Non-limitingexamples of hydrophilic surfactants include non-ionic surfactants, ionicsurfactants and zwitterionic surfactants. Specifically the hydrophilicsurfactants suitable for the current invention include, but not limitedto alcohol-oil transesterification products; polyoxyethylenehydrogenated vegetable oils; polyoxyethylene vegetable oils; alkylsulphate salts, dioctyl sulfosuccinate salts; polyethylene glycol fattyacids esters; polyethylene glycol fatty acids mono- and di-estermixtures; polysorbates, polyethylene glycol derivatives of tocopheroland the like It should be noted that the combinations of two or morehydrophilic surfactants from the same or different classes are withinthe scope of this invention and are together can be referred to as thehydrophilic surfactant unless explicitly specified. In one embodiment,the hydrophilic additive can be a hydrophilic surfactant. Non-limitingexamples of hydrophilic surfactants can include PEG-8 caprylic/capricglycerides, lauroyl macrogol-32 glyceride, stearoyl macrogol glyceride,PEG-40 hydrogenated castor oil, PEG-35 hydrogenated castor oil, sodiumlauryl sulfate, sodium dioctyl sulfosuccinate, polyethylene glycol fattyacids mono- and di-ester mixtures, polysorbate 80, polysorbate 20,polyethylene glycol 1000 tocopherol succinate, phytosterols, phytosterolfatty acid esters, lanosterol PEG-24 cholesterol ether (e.g. SolulanC-24, Amerchol), PEG-30 soya sterol (e.g. Nikkol BPS-30, from Nikko),PEG-25 phyto sterol (e.g. Nikkol BPSH-25 from Nikko), PEG-30 cholestanol(e.g. Nikkol DHC, from Nikko), and mixtures thereof.

In another aspect, other additives described herein in the oral dosageforms (e.g. powder, granulate, particulate, bead, pellet, sprinkle,suspension, solution, tablet, or capsule) can include binders,bufferants, diluents, disintegrants, flavors, colorants, taste-maskingagents, resins, pH modifiers, lubricants, glidants, thickening agent,opacifying agent, humectants, desiccants, effervescing agents,plasticizing agents, antioxidants, solidifying agents, control releaseagents, and the like.

For example, a solidifying agent is a pharmaceutically acceptableadditive that is in a solid physical state at room temperature.Typically solidifying agents facilitate the solidification of thepharmaceutical compositions of the present invention at temperaturesaround room temperature. The compositions and capsule fill of thepresent invention, including those with solidifying agents, can benon-liquid at standard temperature and pressure. In an aspect, thecomposition and capsule fill can be semi-solid or solid at standardtemperature and pressure. When present, the solidifying agent cancomprise from about 0.1 wt % to about 20 wt % of the pharmaceuticalcomposition or capsule dosage form. In one embodiment, the solidifyingagent can melt at a temperature of about body temperature to about 75°C. Non-limiting examples of solidifying agents include polyethyleneglycols; sorbitol; gelatin; stearic acid; cetyl alcohol; cetosteraylalcohol; paraffin wax; polyvinyl alcohol; glyceryl stearates; glyceryldistearate; glyceryl monostearate; glyceryl palmitostearate; glycerylbehenate; waxes; hydrogenated castor oil; hydrogenated vegetable oil;Vit E derivatives, bees wax, microcrystalline wax; sterols;phytosterols; phytosterols fatty acid esters, cholesterol and mixturesthereof. In one embodiment, the solidifying agent includes apolyethylene glycol (PEG) having molecular weight from about 1000 toabout 20,000 and their mixtures. In another embodiment the solidifyingagent includes one or more selected from the group consisting ofpolyethylene glycol; gelatin; stearic acid; polyvinyl alcohol; glycerylstearates; glyceryl distearate; glyceryl monostearate; glycerylpalmitostearate; hydrogenated castor oil; hydrogenated vegetable oil andcholesterol. In an additional embodiment, the solidifying agent includesVit E tocopherol PEG 1000 succinate or derivatives of D-α-TPGS. In oneembodiment, the pharmaceutical composition can be a solid at about roomtemperature. In yet a further embodiment, a “not dissolved” crystallinetestosterone ester can act as a solidifying agent.

The oral compositions of the present invention can be formulated to takeany dosage form commonly known in the pharmaceutical arts such asgranules, tablet or capsule. In one embodiment, the oral pharmaceuticalcompositions of the present invention can be formulated as oral dosageforms such as capsules or tablets. The capsule size can be any sizeknown in the art and can vary depending on the desired dosage amount.For instance, in one embodiment, the capsule can be a hard gelatincapsule having a fill volume of about 0.25 mL to about 1.1 mL.Similarly, in another embodiment, the capsule can be a soft gelatincapsule having a fill volume of about 0.25 mL to about 1.5 mL.

In a specific embodiment, the compositions of the current invention canbe formulated in the form of granules, powder mixtures or tablets. In aspecific embodiment, the testosterone ester present in the dosage formcan be present in the form of nanoparticles or amorphous particles,liquid, or mixtures thereof. In another specific embodiment, thetestosterone ester present in these dosage form can be present in theform of crystalline, non-crystalline or amorphous particles or amixtures thereof having an average particle size of about 2000 nm orless, 1500 nm or less, 1000 nm, 800 nm or less, 600 nm or less, 500 nmor less, 400 nm or less, 300 nm or less, 250 nm or less, 200 nm or less,100 nm or less, 50 nm or less, or 25 nm or less; or the average particlesize of said crystalline, non-crystalline or amorphous particles or amixtures thereof is in the range 10 nm to 2000 nm, 10 nm to 1500 nm, 10nm to 1000 nm, 10 nm to 800 nm, 10 nm to 750 nm; 10 nm to 600 nm, 10 nmto 500 nm, 10 nm to 400 nm, 10 nm to 300 nm, 10 nm to 250 nm, 10 nm to200 nm, or 10 nm to 100 nm.

T13 Dosage Form Examples Containing Exemplary Compositions

Example A Ingredient Dosage Form A1 Dosage Form A2 Name % w/w mg/unit %w/w mg/unit Testosterone Tridecanoate 10-20 140-300 10-15 140-195Pharmaceutical Lipophilic e.g. Castor oil — — 48-55 600-850 acceptableadditives* e.g. Oleic acid 80-90  900-1400 — — carriers e.g. Propylene —— 30-40 400-600 glycol monolaurate Other additives** (e.g.  0-10  0-100 0-12  0-120 antioxidant, solidifer,etc) Total 100 1000-1650 1001000-1650 *Lipophilic additives used in these compositions (e.g. castoroil, oleic acid, and propylene glycol monolaurate) can be replaced withother lipophilic additives or combinations described in the abovecontexts. This can be applied to all other examples. **Other additivesexemplified as antioxidant or solidifer in these compositions can bereplaced with different other additives or combinations described in theabove contexts. This can be applied to all other examples.

Example B Ingredient Dosage Form B1 Dosage Form B2 Dosage Form B3 Name %w/w mg/unit % w/w mg/unit % w/w mg/unit Testosterone Tridecanoate 13-18140-200 25-32 200-300 18-25 140-300 Pharmaceutical LipophilicMono/diglyceride 60-65 575-830 — — — — acceptable additives* 1 (e.g.Glyceryl carriers monolinoleate) Mono/diglyceride — — 4-8 50-80 — — 2(e.g. Glyceryl distearate) Fatty acid1 (e.g. — — 50-60 350-550 45-55350-800 Oleic acid) Fatty acid2 (e.g. — — 2-6 25-40 — — Stearic acid)Triglyceride1 (e.g. — — — —  8-12  70-155 Borage oil) Triglyceride2(e.g. — — — — 2-4 15-40 Peppermint oil) Hydrophilic additives** (e.g.13-17 140-210 2-6 25-40 14-18 110-250 Polyoxyl 40 hydrogenated castoroil) Other Solidifiers (e.g. 4-8 50-80 — — — — additives*** PEG)Antioxidant  0-0.3 0-4  0-0.3 0-4  0-0.3 0-4 Total 100  850-1350 100 650-1200 100  900-1550 *Lipophilic additives used in these compositionscan be replaced with other lipophilic additives or combinationsdescribed in the above contexts. This can be applied to all otherexamples. *Hydrophilic additives used in these compositions (e.g.polyoxyl 40 hydrogenated castor oil) can be replaced with otherhydrophilic additives or combinations described in the above contexts.This can be applied to all other examples. ***Other additivesexemplified as solidifier and antioxidant in these compositions can bereplaced with different other additives or combinations described in theabove contexts. This can be applied to all other examples.

Example C Ingredient Dosage Form C1 Dosage Form C2 Dosage Form C3 Name %w/w mg/unit % w/w mg/unit % w/w mg/unit Testosterone Tridecanoate 10-15140-200 10-15 140-200 10-15 140-200 Pharmaceutical LipophilicTriglyceride 22-28 300-450 — — — — acceptable additives* (e.g. Castorcarriers oil) Fatty acid — — 24-30 300-470 24-30 300-470 (Oleic acid)Mono/diglyceride 15-18 200-300 — — — — derivative (e.g. Propylene glycolmonolaurate) Mono/diglyceride — — — — 12-15 150-240 (e.g. Glyceryldistearate) Monoglyceride — — 14-18 180-280  5-10 100-170 (e.g. Glycerylmonooleate) Glyceride 10-15 150-230 10-15 130-225 4-6  50-100 derivative(e.g. Oleoyl polyoxyl-6 glycerides) Lipophilic 0.5-1.5  5-15 0.5-1.5 5-15 0.5-1.5  5-15 surfactant (e.g. Lecithin) Lipophilic 1-3 25-40 1-325-40 1-3 25-40 surfactant (e.g. Phytosterol) Hydrophilic e.g. Polyoxyl25-35 350-525  6-12 110-185  6-12 110-185 additives** 40 hydrogenatedcastor oil e.g. — — 18-22 230-350 18-22 230-350 Polysorbate 80 e.g. D-α-— — 1-3 20-40 1-3 20-40 tocopherol Other Control release 0.5-1.5  5-150.5-1.5  5-15 0.5-1.5  5-15 additives*** agent Antioxidant  0-0.3  0-1.0 0-0.3  0-1.0  0-0.3  0-10 Total 100 1000-1600 100 1000-1600 1001000-1600 *Lipophilic additives used in these compositions can bereplaced with other lipophilic additives or combinations described inthe above contexts. This can be applied to all other compositions.*Hydrophilic additives used in these compositions can be replaced withother hydrophilic additives or combinations described in the abovecontexts. This can be applied to all other compositions. ***Otheradditives used in these compositions can be replaced with differentother additives or combinations described in the above contexts. Thiscan be applied to all other compositions.Non-limiting examples of dosing regimen for oral TRT with dosage formscontaining compositions of this invention comprising TT are describedbelow:

Single Fixed Dose Dosing Regimen Examples for Safety with food with atleast 10 g of fat Cmax > 1500 ng/dL Cmax > 1800 ng/dL Cmax > 2500 ng/dLRegimen T13 Dose <20% <15% <10% <5% <2% none of Category # (mg)patitents patients patitents patients patitents patients QD 1 500 YesYes Yes Yes Yes Yes 2 700 Yes Yes Yes Yes Yes Yes 3 750 Yes Yes Yes YesYes Yes 4 800 Yes Yes Yes Yes Yes Yes 5 900 Yes Yes Yes Yes Yes Yes 61000 Yes Yes Yes Yes Yes Yes 7 1100 Yes Yes Yes Yes Yes Yes 8 1150 YesNo Yes Yes Yes No 9 1250 No No No No No No BID-equal 10 250/250 Yes YesYes Yes Yes Yes dose 11 350/350 Yes Yes Yes Yes Yes Yes (AM/PM) 12375/375 Yes Yes Yes Yes Yes Yes 13 400/400 Yes Yes Yes Yes Yes Yes 14450/450 Yes Yes Yes Yes Yes Yes 15 500/500 Yes Yes Yes Yes Yes Yes 16550/550 Yes Yes Yes Yes Yes Yes 17 575/575 Yes Yes Yes Yes Yes Yes 18625/625 Yes Yes Yes Yes Yes Yes

Single Fixed Dose Dosing Regimen Examples for Efficacy with food with atleast 10 g of fat Regimen T13 Dose Cavg > 300 ng/dL Category # (mg) ≥80%patients ≥75% patients QD 1 500 No No 2 700 No No 3 750 No Yes 4 800 YesYes 5 900 Yes Yes 6 1000 Yes Yes 7 1100 Yes Yes 8 1150 Yes Yes 9 1250Yes Yes BID-equal 10 250/250 No No dose 11 350/350 No No (AM/PM) 12375/375 No Yes 13 400/400 Yes Yes 14 450/450 Yes Yes 15 500/500 Yes Yes16 550/550 Yes Yes 17 575/575 Yes Yes 18 625/625 Yes Yes

Dosage Form Example B of Composition 4 with dosing regimen (Regimen #.1-9) of dosing category BID-equal dose with daily dose range 500-1250 mgof T13 in this invention were used for a clinic study of TestosteroneTherapy for hypogonadal males.

The Clinical Study is following as

This Clinical Study is a Randomized Double-Blind, Placebo-ControlledDose Escalating Study of the Safety, Efficacy, Tolerability, andPharmacokinetics of Testosterone Therapy in Hypogonadal Males. Thisclinic study was a single and multiple, ascending-dose study that wasdesigned to determine the optimal starting, titration (if appropriate),or single fixed dose for safety and efficacy targeted by US FDA. Thestudy also verified the time for testosterone levels to reach steadystate and identified a suitable single fixed dose dosing regimen thatsatisfies unmet need for safety and efficacy for oral TRT.

This study was carried out with conditions of a single-center,randomized, double-blind, placebo-controlled, ascending multiple-dose,and serial-group in adult hypogonadal male subjects. The objectives ofthis study were:

-   -   a) To assess the safety, efficacy, and tolerability of        escalating single and multiple oral doses of T13 dosage forms in        hypogonadal males    -   b) To determine the pharmacokinetics (PK) of testosterone (T),        DHT, TT, DHTT, and estradiol (E2) after single and multiple oral        doses of TT dosage forms in hypogonadal males    -   c) To identify single fixed dose dosing regimen satisfying USFDA        target, not needing to titrate for restoring average serum T        levels in hypogonadal males to the normal T range.

The following sections summarize the critical elements of the study andpertinent clinical pharmacology results.

The dosing regimen for this clinic study ranged from 500 mg daily doseto 1250 mg daily dose with once a day dosing. Observed pharmacokineticparameters (T, DHT, T13, DHTT, and E2) after single and multiple oraldoses of T13 dosage forms in the patients were recorded by each dailydose in the report. Further analysis to identify single fixed dosedosing regimen that does not need to titrate for safety and efficacy wascarried out based on the criteria targeted by USFDA. For example, thepharmacokinetic parameters of T level after administration of dosingregimens for 1) 750 mg T13 QD and 2) 1000 mg T13 QD daily doses weremeasured and analyzed according to the criteria targeted by US FDA as

-   -   T Cavg/day>300 ng/dL should be more than 75% of patients        -   1) 750 mg T13 QD dosing regimen resulted in 76.2% of            patients with T Cavg/day>300 ng/dL; Cavg (±SD) for 750 mg            T13 QD dose at steady state (14 days) is 352 (±41) ng/dL.        -   2) 1000 mg T3 QD dosing regimen resulted in 88.1% of            patients with T Cavg/day>300 ng/Dl; Cavg (±SD) for 1000 mg            TT QD dose at steady state (14 days) is 405 (±148) ng/dL.    -   T Cmax/dose<1,500 ng/dL should be more than 85% of patients        -   1) 750 mg T13 QD dosing regimen resulted in 99.5% of            patients with T Cmax/dose<1,500 ng/dL; Cmax (±SD) for 750 mg            T13 QD dose at steady state (14 days) is 822 (±254) ng/dL.        -   2) 1000 mg T13 QD dosing regimen resulted in 92.8% of            patients with T Cmax/day<1,500 ng/Dl; Cmax (±SD) for 1000 mg            T13 QD dose at steady state (14 days) is 930 (±326) ng/dL.

The overall analyzed results of this clinic study were plotted accordingto % of patients for safety (Cmax<1,500 ng/dL) and efficacy (Cavg>300ng/dL) with a variety of dosing regimen. Its results are shown in thebelow table.

Clinical Trial Results for % Patients for the Cavg Criteria with VariousDaily Dose Daily dose Equivalent T Dose % with Cavg/day > 300 (mg) (mg)ng/dL* 500 298 36.3 700 417 71.5 750 446 76.2 800 476 80.0 900 536 85.01000 595 88.1 1100 655 90.0 1150 685 90.7 1250 744 91.6 *Bold letterssatisfy that % patients for Cavg/day > 300 ng/dL is more than 75%.

Clinical Trial Results for % Patients for the Cmax Criteria with VariousDaily Dose Daily dose Equivalent T Dose % with Cmax/dose < 1,500 (mg)(mg) ng/dL** 500 298 100.0 700 417 100.0 750 446 99.5 800 476 98.8 900536 96.7 1000 595 92.8 1100 655 85.6 1150 685 80.0 1250 744 66.8 *Boldletters satisfy that % patients for Cmax/dose < 1,500 ng/dL is more than85%.

In conclusion, the single fixed dose dosing regimen of oral T13 dosewith no need to titrate (or dose adjust) ranges from 750 mg daily doseto 1100 mg daily dose of T13, which satisfies US FDA T level target forsafety and efficacy for testosterone replacement therapy.

1. A method of restoring serum testosterone levels to a normal eugonadalrange in a male having a condition associated with a deficiency orabsence of endogenous testosterone, comprising orally administering apharmaceutical composition comprising a therapeutically effective amountof testosterone tridecanoate (T13) in a fixed dose administrationregimen with food.
 2. The method of claim 1, wherein the compositionfurther comprises an additive.
 3. The method of claim 1, wherein thefixed dose administration regimen provides a total daily dose of T13 offrom 750-1150 mg.
 4. The method of claim 1, wherein the fixed doseadministration regimen comprises administering said composition once ortwice daily.
 5. The method of claim 1, wherein said composition is inthe form of a hard or soft capsule.
 6. The method of claim 1, wherein aunit dosage form of the composition comprises about 100-500 mg T13. 7.The method of claim 1, further comprising measuring a therapydiscontinuation criterion that indicates an advised discontinuation oftherapy where serum testosterone (T) levels are consistently >2500ng/dl.
 8. A method of restoring daily average serum testosterone(C_(avg)) to a normal eugonadal range in at least 75% of males in apopulation having a condition associated with a deficiency or absence ofendogenous testosterone, comprising oral administration of an oraldosage form comprising a therapeutically effective amount oftestosterone tridecanoate (T13) in a fixed dose administration regimenwith food.
 9. The method of claim 8, wherein the oral dosage formfurther comprises an additive.
 10. The method of claim 8, wherein thefixed dose administration regimen provides a total daily T13 dose offrom 750-1150 mg.
 11. The method of claim 8, wherein the fixed doseadministration regimen comprises administering said oral dosage formonce or twice daily.
 12. The method of claim 8, wherein said dosage formis in the form of a hard or soft capsule.
 13. The method of claim 8,wherein the therapeutically effective amount is about 100-500 mg. 14.The method of claim 8, further comprising measuring a therapydiscontinuation criterion that indicates an advised discontinuation oftherapy where serum T levels are consistently >2500 ng/dl.
 15. A methodof treating a condition associated with a deficiency or absence ofendogenous testosterone in a male patient, comprising: orallyadministering a fixed dose of 375-575 mg of testosterone tridecanoate(T13) twice daily or 750-1150 mg once daily in a fixed dose dosingregimen with food.
 16. The method of claim 15, wherein the fixed doseprovides from 800-1100 mg testosterone tridecanoate per day.
 17. Themethod of claim 15, wherein the fixed dose provides from 900-1100 mgtestosterone tridecanoate per day.
 18. The method of claim 15, whereinthe fixed dose provides from 925-1075 mg testosterone tridecanoate perdose.
 19. The method of claim 15, wherein the fixed dose provides from950-1050 mg testosterone tridecanoate per dose.
 20. The method of claim15, wherein the fixed dose provides from 975-1025 mg testosteronetridecanoate per dose. 21-42. (canceled)